New Definition Criteria of Myocardial Dysfunction in Patients with Liver Cirrhosis: A Speckle Tracking and Tissue Doppler Imaging Study

There are no clear recommendations regarding cirrhotic cardiomyopathy (CC) evaluation in patients with pre-transplant liver cirrhosis. The roles of new methods, tissue Doppler imaging (TDI) and speckle tracking echocardiography (STE) in the diagnosis and prognosis of cirrhotic cardiomyopathy remain controversial. We investigated the utility of TDI/STE parameters in cirrhotic cardiomyopathy diagnosis and also in predicting mortality in patients with liver cirrhosis. Left/right ventricular function was studied using conventional TDI (velocities) and STE (strain/strain rate). We assessed left ventricular diastolic dysfunction, graded into four new classes (I/Ia/II/III). Serum NTproBNP (N-terminal prohormone of brain natriuretic peptide), troponin I, β-crosslaps, QTc interval, arterial compliance and endothelial function were measured. Liver-specific scores (Child–Pugh, MELD, MELDNa) were computed. There was a 1-y follow-up visit to determine mortality. We observed resting biventricular diastolic myocardial dysfunction, not presently included in the definition of cirrhotic cardiomyopathy. We provided an improved characterization of cardiac dysfunction in patients with liver cirrhosis. This might change the current definition. However, the utility of STE/TDI parameters in predicting long-term mortality in patients with liver cirrhosis remains controversial.     

p.H282N and p.Y191H: 2 novel CYP21A2 mutations in Italian congenital adrenal hyperplasia patients

More than 90% of all cases of congenital adrenal hyperplasia (CAH) result from steroid 21-hydroxylase gene (CYP21A2) mutations. The CYP21A2 gene is located in the human leukocyte antigen (HLA) class III region on the short arm of chromosome 6p21.3, along with an inactive pseudogene, CYP21A1P, that is 98% homologous in its coding sequence with CYP21A2. Most CYP21A2 mutations result from intergenic recombinations between CYP21A2 and the closely linked CYP21A1P pseudogene. Rare mutations not generated by gene conversion account for only 5% to 10% of 21-hydroxylase deficiency alleles. However, detection of these rare and spontaneous mutations has continued to expand worldwide. We identified 2 novel CYP21A2 missense mutations (p.H282N and p.Y191H) in 2 Italian patients with simple-virilizing and nonclassic CAH forms. Functional analysis of these CYP21A2 mutations was performed. Functional in vitro assay for mutagenized CYP21A2 enzymes was performed in transiently transfected mammalian cells to test the residual enzyme activity and the apparent kinetic values. The residual activities obtained allowed us to classify the p.H282N and p.Y191H variants as simple-virilizing and nonclassic CAH associated mutations, respectively. These results correlate with the rate of severity of the patients' disease. This finding provides a further contribution for assisting in the diagnosis of CAH patients.